Genomics and proteomics research made a vast number of nucleotide and peptide sequences available for analysis. Consequently, high-throughput screening of samples for the presence and/or quantity of a vast number of known genes or polypeptides has gained considerable interest in recent years. There are various devices and methods known in the art, and many of those devices and methods are adapted for screening of multiple nucleic acid sequences.
For example, in a relatively simple approach, Johann et al describe in U.S. Pat. No. 6,277,628 a test system in which a plurality of carrier structures is enclosed in a capillary, and wherein at least some of the carrier structures (e.g., glass beads) are covalently coated with a biomolecular probe. Johann's system advantageously reduces the ratio of sample volume to test surface, thereby reducing potential delays due to kinetic effects. However, various problems arise with the use of such systems. Among other disadvantages, optical detection (e.g., fluorescence) of a signal from a hybridized probe is at least to some degree impaired by inadvertent absorption of light (e.g., excitation and emission) by the capillary. Furthermore, intrinsic optical effects (e.g., auto-fluorescence) of the capillary will likely further reduce sensitivity of the assay or method. Still further, inadvertent focusing/diffusion of incident and/or emitted light is almost unavoidable due to the strong curvature of the capillary. Moreover, assembly of Johann's test systems is relatively tedious and time consuming.
In another example, hybridization of target molecules from a sample to an immobilized capture probe is accelerated by electrophoretic assistance using a microchip-type device as described in U.S. Pat. Nos. 5,632,957, 5,605,662, and 5,849,486. Use of such microchip devices not only increases the speed of molecular association between a target molecule and a capture probe, but also allows addressability of each “pixel” of the test array. Furthermore, stringency may be electronically regulated in a relatively simple manner in a reverse process to electrophoretically assisted hybridization. However, the sample density of such devices in many commercially available systems is typically limited to about 100 pixels per device. Moreover, electrophoretically assisted hybridization requires use of complex and relatively expensive chips, and loading/hybridization and detection are typically performed using separate instruments, thereby further increasing initial, operating, and maintenance expenses.
In a further example, test arrays are produced using a photolithographic process, thereby allowing relatively high density of capture probes (e.g., greater than 10000 probes per array). Systems for such high-density arrays are described, for example, in U.S. Pat. Nos. 5,599,695, 5,843,655, and 5,631,734. While high-density arrays are particularly useful for sequencing or complex genetic analysis, numerous disadvantages remain. For example, custom synthesis of such high-density arrays is likely cost-prohibitive for all but a few individuals and/or organizations. Furthermore, high-density arrays will often have limited applications in routine clinical diagnostics. Moreover, due to the particular chemistry employed in building such arrays, non-nucleic acid probes (e.g., receptors, antibodies, and other polypeptides) are difficult, if at all, to implement.
Thus, although numerous multi-substrate arrays are known in the art, all or almost all of them suffer from one or more disadvantage (e.g., high cost, difficult to customize, specialized chemistry, etc.). Therefore, there is still a need to provide improved multi-substrate array devices and methods.